Advanced maternal age was associated with an annual decline in reproductive success despite use of donor oocytes: A retrospective study.

OBJECTIVE To study if there is an increasing risk of poor reproductive outcomes associated with age in IVF patients using donor oocytes and when it becomes clinically relevant. DESIGN Multicenter, retrospective cohort study SUBJECTS: IVF patients ≥35 years at 19 private fertility clinics in Spain. EXPOSURE A single day 5 embryo from a donor oocyte (<35 years) transferred to the IVF patient undergoing a hormone replacement therapy, between February 2000 and September 2022. MAIN OUTCOME MEASURES Live birth, implantation failure, and pregnancy loss rates were analyzed using a continuous scale of women's ages to determine the gradual effect of age that is clinically relevant. The relative risks of pregnancy loss and implantation failure after 40 years of age were calculated adjusting for body mass index, IVF cycle parameters, and the embryo's developmental stage and euploidy. RESULTS Analysis of 33,141 good-quality, single embryo transfers identified the maternal age where reproductive rates worsened as 39, 40 and 43 years for implantation failure, live birth, and pregnancy loss rates, respectively. Before live birth rates drastically decreased, there was no significant increment in the relative risk for negative outcomes (p-value>0.05). Nevertheless, after the age of 40, the relative risk of implantation failure increased by 4.2% per year (RR = 1.042, 95% CI: 1.028-1.056; p-value <0.0001) while that of pregnancy loss increased by 3.2% per year (RR = 1.032, 95% CI: 1.013-1.051; p-value = 0.0007). CONCLUSION Challenging traditional paradigms that embryo factors drive the detrimental effect of age on reproductive outcomes, this study reveals that uterine age may also play a significant role in age-related detrimental effects. Given that embryo factors were controlled for, these findings suggest that the worsening of reproductive outcomes associated to the effects of age in the uterus. In addition, this study design identified the specific age at which the live birth rate decreases, and implantation failure rate and pregnancy loss rate increases. Our results encourage further study of how uterine age annually impacts pregnancy rates and support the uterus becoming a potential target for antiaging therapies aiming to improve outcomes of assisted reproductive technologies.